ProphARG | Evolution of Prophages that carry Antibiotic Resistance Genes (ARGs) and their host-bacteria in response to antibiotics and increased lytic activity

Summary
In the European Union, 25,000 deaths per year are caused by multidrug resistant bacteria. This trend is predicted to increase with ever increasing misuse and overuse of antibiotics, which accelerates the evolution of antibiotic resistance (AR). An important mechanism of transferring antibiotic resistance genes (ARGs) among bacteria are temperate bacteriophages (prophages), viruses that can incorporate their own genetic material into the bacterial chromosome, thereby providing their bacterial host (which is now called a ‘lysogen’) with additional genes, such as ARGs. Despite their vast abundance in nature, our understanding of the evolution of ARG-carrying prophages is still incomplete. Therefore I will study the evolution of ARG-carrying prophages and their host bacteria. Specifically, using constructed lysogens (carrying prophage lambda+ARG) of E. coli bacteria, I will (1) use competitive fitness assays to determine the costs/benefits for bacteria of carrying prophages that encode AR and how these costs depend on environmental antibiotic concentrations and the frequency with which the prophage enters the lytic cycle (i.e. the prophage becomes active, replicates and lyses the host cell). (2) I will follow the evolution of these lysogens that carry AR-encoding prophages using a serial transfer experiment in the presence/absence of antibiotics and compounds that induce phage lysis. (3) I will sequence the evolved lysogens including their prophage genomes to detect underlying genomic changes associated with bacterial adaptation to prophage carriage. I predict that the net effect of a prophage that encodes an ARG on the growth and evolution of its host bacterium will strongly depend on both the frequency with which the phage enters the lytic cycle and the costs/benefits of the ARG. By using a novel approach that has been neglected so far (evolution of ARG-carrying prophages) this project will improve our understanding of AR evolution.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/794447
Start date: 01-09-2018
End date: 31-08-2020
Total budget - Public funding: 187 419,60 Euro - 187 419,00 Euro
Cordis data

Original description

In the European Union, 25,000 deaths per year are caused by multidrug resistant bacteria. This trend is predicted to increase with ever increasing misuse and overuse of antibiotics, which accelerates the evolution of antibiotic resistance (AR). An important mechanism of transferring antibiotic resistance genes (ARGs) among bacteria are temperate bacteriophages (prophages), viruses that can incorporate their own genetic material into the bacterial chromosome, thereby providing their bacterial host (which is now called a ‘lysogen’) with additional genes, such as ARGs. Despite their vast abundance in nature, our understanding of the evolution of ARG-carrying prophages is still incomplete. Therefore I will study the evolution of ARG-carrying prophages and their host bacteria. Specifically, using constructed lysogens (carrying prophage lambda+ARG) of E. coli bacteria, I will (1) use competitive fitness assays to determine the costs/benefits for bacteria of carrying prophages that encode AR and how these costs depend on environmental antibiotic concentrations and the frequency with which the prophage enters the lytic cycle (i.e. the prophage becomes active, replicates and lyses the host cell). (2) I will follow the evolution of these lysogens that carry AR-encoding prophages using a serial transfer experiment in the presence/absence of antibiotics and compounds that induce phage lysis. (3) I will sequence the evolved lysogens including their prophage genomes to detect underlying genomic changes associated with bacterial adaptation to prophage carriage. I predict that the net effect of a prophage that encodes an ARG on the growth and evolution of its host bacterium will strongly depend on both the frequency with which the phage enters the lytic cycle and the costs/benefits of the ARG. By using a novel approach that has been neglected so far (evolution of ARG-carrying prophages) this project will improve our understanding of AR evolution.

Status

CLOSED

Call topic

MSCA-IF-2017

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2017
MSCA-IF-2017